Department Experimental Immunology, Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
PLoS One. 2013;8(1):e54684. doi: 10.1371/journal.pone.0054684. Epub 2013 Jan 23.
Broadly neutralizing antibodies may protect against HIV-1 acquisition. In natural infection, only 10-30% of patients have cross-reactive neutralizing humoral immunity which may relate to viral and or host factors. To explore the role of host genetic markers in the formation of cross-reactive neutralizing activity (CrNA) in HIV-1 infected individuals, we performed a genome-wide association study (GWAS), in participants of the Amsterdam Cohort Studies with known CrNA in their sera. Single-nucleotide polymorphisms (SNPs) with the strongest P-values are located in the major histocompatibility complex (MHC) region, close to MICA (P = 7.68 × 10(-7)), HLA-B (P = 6.96 × 10(-6)) and in the coding region of HCP5 (P = 1.34 × 10(-5)). However, none of the signals reached genome-wide significance. Our findings underline the potential involvement of genes close or within the MHC region with the development of CrNA.
广谱中和抗体可能有助于预防 HIV-1 感染。在自然感染中，只有 10-30%的患者具有交叉反应性中和体液免疫，这可能与病毒和/或宿主因素有关。为了探索宿主遗传标记在 HIV-1 感染个体中形成交叉反应性中和活性 (CrNA) 的作用，我们对阿姆斯特丹队列研究中的参与者进行了全基因组关联研究 (GWAS)，这些参与者的血清中已知存在 CrNA。具有最强 P 值的单核苷酸多态性 (SNP) 位于主要组织相容性复合体 (MHC) 区域，靠近 MIC A (P = 7.68×10(-7))、HLA-B (P = 6.96×10(-6)) 和 HCP5 的编码区域 (P = 1.34×10(-5))。然而，没有一个信号达到全基因组显著水平。我们的研究结果强调了 MHC 区域附近或内部的基因在 CrNA 发展中的潜在作用。
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